Steroid hormones, synthesized and secreted into the bloodstream by endocrine glands, are vital constituents for the proper functioning of the human body. Steroid hormones can be classified into five groups based on the receptors to which they bind, namely: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. It is known that steroid hormones aid in regulating metabolism, regulating water and salt function, regulating immune function, controlling inflammation, and developing sexual characteristics. Steroid hormones such as progesterone and estradiol have poor bioavailability and efficacy as these hormones are less soluble in water. Thus, these hormones need to be administered in a high dose, which can result in increased health risks.
Progesterone is a naturally occurring C-21 steroid hormone belonging to the progestogen class. It is produced by the ovaries (more precisely by the cells of the corpus luteum) during the post-ovulatory luteal phase and to a lesser degree by the adrenal glands and the placenta during the second part of pregnancy. In women, progesterone levels are relatively low during the pre-ovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase. Progesterone is commonly referred to as the “hormone of pregnancy” as it plays an important role in fetal development. Insufficient secretion of progesterone in women can cause biological effects such as progestative effect, anti-androgen effect, and anti-estrogen effect. Further, progesterone insufficiency can lead to premenstrual syndromes and menstrual irregularities.
Progesterone and its analogues are used to support pregnancy in Assisted Reproductive Technology (ART) cycles, to control persistent ovulatory bleeding, to prepare the uterine lining in infertility therapy, and to support early pregnancy. Further, progesterone can be used for regularizing menstruation. Vaginally dosed progesterone is also being investigated for a potentially beneficial treatment in preventing preterm birth in women who are at the risk of preterm birth.
Progesterone does not dissolve in water and is poorly absorbed resulting in both intra- and inter-patient variability when orally administered. To overcome the drawbacks of poor bioavailability associated with natural progesterone, researchers have used various synthetic progesterone derivatives such as medroxyprogesterone, norethisterone, methylestrenolone, chlormadinone acetate, 6-dehydroretroprogesterone, and lynestrenol. But use of these derivatives are associated with side-effects not associated with natural progesterone.
U.S. Pat. Nos. 4,196,188; 5,140,021; 7,431,941; 7,829,115; and U.S. Patent Application Publication No. 2011/0135719 are hereby incorporated by reference.